Limits...
Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis

View Article: PubMed Central - PubMed

ABSTRACT

Although cisplatin is an effective anti-cancer agent that is widely used for treating various types of malignant solid tumors, the nephrotoxicity induced by cisplatin severely limits its clinical application. The present study was designed to explore the potential protective effect of ginsenoside Rg5, a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity in a mouse experimental model. The possible mechanisms underlying this nephroprotective effect were also investigated for the first time. Rg5 was given at doses of 10 and 20 mg/kg for 10 consecutive days. On Day 7, a single nephrotoxic dose of cisplatin (25 mg/kg) was injected to mice. Cisplatin administration resulted in renal dysfunction as evidenced by increase in serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, cisplatin increased the level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the makers of lipid peroxidation, and depleted glutathione (GSH) content and superoxide dismutase (SOD) activity in renal tissues. These effects were associated with the significantly increased levels of cytochrome P450 E1 (CYP2E1), 4-hydroxynonenal (4-HNE), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in renal tissues. However, pretreatment with ginsenoside Rg5 significantly attenuated the renal dysfunction, oxidative stress and inflammation response induced by cisplatin. Furthermore, ginsenoside Rg5 supplementation inhibited activation of apoptotic pathways through increasing Bcl-2 and decreasing Bax expression levels. Histopathological examination further confirmed the nephroprotective effect of Rg5. Collectively, these results clearly suggest that Rg5-mediated alleviation of cisplatin-induced nephrotoxicity may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

No MeSH data available.


Related in: MedlinePlus

Effect of Rg5 on the levels of renal inflammatory cytokines in cisplatin-induced nephrotoxicity. The levels of: tumor necrosis factor (TNF)-α (A); and interleukin (IL)-1β (B) in kidney tissues were determined by ELISA kits. All data were expressed as mean ± S.D., n = 8. ** p < 0.01 vs. normal group; #p < 0.05, ##p < 0.01 vs. cisplatin group.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5037551&req=5

nutrients-08-00566-f006: Effect of Rg5 on the levels of renal inflammatory cytokines in cisplatin-induced nephrotoxicity. The levels of: tumor necrosis factor (TNF)-α (A); and interleukin (IL)-1β (B) in kidney tissues were determined by ELISA kits. All data were expressed as mean ± S.D., n = 8. ** p < 0.01 vs. normal group; #p < 0.05, ##p < 0.01 vs. cisplatin group.

Mentions: Previous studies indicated that oxidative stress is known to be associated with release of pro-inflammatory cytokine such as TNF-α and IL-1β in cisplatin-induced nephrotoxicity [28]. In the present study, the levels of TNF-α and IL-1β in kidney tissues were determined by ELISA. As indicated in Figure 6, single cisplatin injection (cisplatin control group) caused markedly higher levels of TNF-α and IL-1β in kidney tissues than those in normal group (p < 0.05). In contrast, pretreatment with ginsenoside Rg5 significantly suppressed the production of TNF-α and IL-1β in a dose-independent manner (p < 0.05).


Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis
Effect of Rg5 on the levels of renal inflammatory cytokines in cisplatin-induced nephrotoxicity. The levels of: tumor necrosis factor (TNF)-α (A); and interleukin (IL)-1β (B) in kidney tissues were determined by ELISA kits. All data were expressed as mean ± S.D., n = 8. ** p < 0.01 vs. normal group; #p < 0.05, ##p < 0.01 vs. cisplatin group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037551&req=5

nutrients-08-00566-f006: Effect of Rg5 on the levels of renal inflammatory cytokines in cisplatin-induced nephrotoxicity. The levels of: tumor necrosis factor (TNF)-α (A); and interleukin (IL)-1β (B) in kidney tissues were determined by ELISA kits. All data were expressed as mean ± S.D., n = 8. ** p < 0.01 vs. normal group; #p < 0.05, ##p < 0.01 vs. cisplatin group.
Mentions: Previous studies indicated that oxidative stress is known to be associated with release of pro-inflammatory cytokine such as TNF-α and IL-1β in cisplatin-induced nephrotoxicity [28]. In the present study, the levels of TNF-α and IL-1β in kidney tissues were determined by ELISA. As indicated in Figure 6, single cisplatin injection (cisplatin control group) caused markedly higher levels of TNF-α and IL-1β in kidney tissues than those in normal group (p < 0.05). In contrast, pretreatment with ginsenoside Rg5 significantly suppressed the production of TNF-α and IL-1β in a dose-independent manner (p < 0.05).

View Article: PubMed Central - PubMed

ABSTRACT

Although cisplatin is an effective anti-cancer agent that is widely used for treating various types of malignant solid tumors, the nephrotoxicity induced by cisplatin severely limits its clinical application. The present study was designed to explore the potential protective effect of ginsenoside Rg5, a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity in a mouse experimental model. The possible mechanisms underlying this nephroprotective effect were also investigated for the first time. Rg5 was given at doses of 10 and 20 mg/kg for 10 consecutive days. On Day 7, a single nephrotoxic dose of cisplatin (25 mg/kg) was injected to mice. Cisplatin administration resulted in renal dysfunction as evidenced by increase in serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, cisplatin increased the level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the makers of lipid peroxidation, and depleted glutathione (GSH) content and superoxide dismutase (SOD) activity in renal tissues. These effects were associated with the significantly increased levels of cytochrome P450 E1 (CYP2E1), 4-hydroxynonenal (4-HNE), tumor necrosis factor (TNF)-&alpha;, interleukin (IL)-1&beta;, nuclear factor-kappa B (NF-&kappa;B) p65, and cyclooxygenase-2 (COX-2) in renal tissues. However, pretreatment with ginsenoside Rg5 significantly attenuated the renal dysfunction, oxidative stress and inflammation response induced by cisplatin. Furthermore, ginsenoside Rg5 supplementation inhibited activation of apoptotic pathways through increasing Bcl-2 and decreasing Bax expression levels. Histopathological examination further confirmed the nephroprotective effect of Rg5. Collectively, these results clearly suggest that Rg5-mediated alleviation of cisplatin-induced nephrotoxicity may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

No MeSH data available.


Related in: MedlinePlus